ID93/GLA-SE Vaccination + BCG Challenge

Inclusion Criteria:

The volunteer must satisfy all the following criteria to be eligible for the study:

• Healthy adults aged 18-55 years

• Resident in or near Oxford for the duration of the study period

• Provide written informed consent

• Willing to allow the investigators to discuss the volunteer's medical history withtheir General Practitioner (or review summary care record, if available)

• Allow the investigator to register volunteer details with a confidential database (The Over-volunteering Protection Service) to prevent concurrent entry into clinicalstudies/trials

• Agreement to refrain from blood donation during the course of the study

• For persons of child-bearing potential only, willingness to practice continuouseffective contraception (see below) during the study and a negative pregnancy teston the day(s) of screening, vaccination, challenge and bronchoscopy

• Able and willing (in the investigator's opinion) to comply with all studyrequirements

• No clinically relevant findings in medical history or on physical examination

• Screening IGRA (interferon gamma release assay) negative

• Willing to be tested for evidence of COVID-19 infection and to allow public healthnotification of the results if required

• EITHER Previously vaccinated with the BCG (at least 12 months prior to enrolment, asevidenced by a visible scar or documentation in medical or occupational healthrecords) OR Never previously vaccinated with BCG and no evidence of BCG scar atphysical examination

Exclusion Criteria:

The volunteer may not enter the study if any of the following apply:

• Participation in another research study involving receipt of an investigationalproduct in the 30 days preceding enrolment or during the trial follow up period

• Any clinically significant respiratory disease, including asthma

• Current smoker (defined as any smoking including e-cigarettes in the last 3 months)

• History of anaphylaxis to vaccination or any allergy likely to be exacerbated by anycomponent of the study agent, any essential study procedure, sedative drugs, or anylocal or general anaesthetic agents

• History of allergic reaction to Kanamycin or kanamycin-related antibiotics

• Clinically significant history of skin disorder, allergy, atopy, cancer (exceptbasal cell carcinoma of the skin or carcinoma in situ of the cervix), bleedingdisorder, cardiovascular disease (including uncontrolled hypertension),gastrointestinal disease, liver disease, renal disease, endocrine disorder,neurological illness, psychiatric disorder, drug or alcohol abuse

• Any significant autoimmune conditions or immunodeficiency (including current HIV)

• Previous diagnosis or treatment for TB disease or latent TB infections

• Clinical, radiological, or laboratory evidence of current active TB disease orlatent TB infection

• Previous receipt of any investigational TB vaccine or aerosolised BCG

• Currently infected with HIV, Hepatitis B or Hepatitis C based on positiveserological testing (Hepatitis B surface antigen, Hepatitis C virus or HIVantibodies) and confirmatory molecular testing if indicated

• Concurrent use of oral, inhaled or systemic steroid medication or use for more than 14 days within the last 6 months (steroids used as a cream or ointment arepermissible), or the use of other immunosuppressive agents concurrently or for morethan 14 days within the last 6 months

• Administration of immunoglobulins and/or any blood products within the three monthspreceding the planned enrolment date

• Administration of a live vaccine within the preceding 28 days prior to enrolment, orplan for such prior to aerosol challenge

• Administration of any other non-live vaccine within the preceding 14 days prior toenrolment

• Current use of any medication or other drug taken through the nasal or inhaled routeincluding cocaine or other recreational drugs

• Any nasal, pharyngeal, or laryngeal finding which precludes bronchoscopy

• Pregnancy, lactation or intention to become pregnant during study period

• Previously resident for more than 12 months concurrently in the rural areas of atropical climate where significant non-tuberculous mycobacterial exposure is likely

• Shares a household with someone with clinically significant immunodeficiency (eitherfrom infection or medication) who is deemed to be at risk of developing disseminatedBCG infection if exposed to BCG

• Clinically significant abnormality on screening chest radiograph

• Clinically significant abnormality of lung function testing

• Any clinically significant abnormality of screening blood or urine tests

• A body mass index (BMI) of <18.5 or >45

• Any other significant disease, disorder, or finding, which, in the opinion of theinvestigator, may either put the volunteer at risk, affect the volunteer's abilityto participate in the study or impair interpretation of the study data